A guide to link and apply biophysics for developing biopharmaceuticals
This book focuses on the application of biophysical techniques and methods in the development of biotherapeutics. Four areas, all focusing on biotherapeutics development, are emphasized (1) novel applications and new methods of traditional biophysical techniques, (2) novel and emerging technologies and their applications, (3) biophysical applications relevant to stage–wise development of a clinical biotherapeutic candidate, and (4) thermodynamic, conformational and stabilization concepts aided by biophysical research.
The chapters are laid out in a theme based on clinical phases of development. This allows for a comprehensive view of:
Which biophysical studies are needed for which stage and for what purpose,
How and when to apply the techniques,
What types of characterization regulatory agencies expect, and
The limitations of each technique and type of application.
Overall, this book helps formulation, analytical, and bioanalytical scientists in pharma and biotech industries better understand and use biophysical methods and assess impact on quality and immunogenicity. It also provides information to help organizations develop short– and long–term strategies for resource investment in biophysical research.
PREFACE VII
ABOUT THE EDITOR IX
CONTRIBUTORS XI
SECTION 1 EARLY DISCOVERY STAGES AND BIOTHERAPEUTIC CANDIDATE SELECTION
1 BIOPHYSICAL METHODS APPLIED IN EARLY DISCOVERY OF A BIOTHERAPEUTIC: CASE STUDY OF AN EGFR–IGF1R BISPECIFIC ADNECTIN 3
Michael L. Doyle, James W. Bryson, Virginie Lafont, Zheng Lin, Paul E. Morin, Lumelle A. Schneeweis, Aaron P. Yamniuk, and Joseph Yanchunas Jr.
2 X–RAY CRYSTALLOGRAPHY FOR BIOTHERAPEUTICS 25
Glen Spraggon
3 SOLUBILITY AND EARLY ASSESSMENT OF STABILITY FOR PROTEIN THERAPEUTICS 65
Sheng–Jiun Wu, Gary L. Gilliland, and Yiqing Feng
SECTION 2 FIRST–IN–HUMAN AND UP TO PROOFOF–CONCEPT CLINICAL TRIALS
4 BIOPHYSICAL AND STRUCTURAL CHARACTERIZATION NEEDED PRIOR TO PROOF OF CONCEPT 95
Angela W. Blake–Haskins, Yen–Huei Lin, Zhuchun Wu, Melissa D. Perkins,and Thomas M. Spitznagel
5 NUCLEATION, AGGREGATION, AND CONFORMATIONAL DISTORTION 125
Christopher J. Roberts
6 UTILIZATION OF CHEMICAL LABELING AND MASS SPECTROMETRY FOR THE BIOPHYSICAL CHARACTERIZATION OF BIOPHARMACEUTICALS 151
Justin B. Sperry and Lisa M. Jones
7 APPLICATION OF BIOPHYSICAL AND HIGH–THROUGHPUT METHODS IN THE PREFORMULATION OF THERAPEUTIC PROTEINS FACTS AND FICTIONS 173
Ahmad M. Abdul–Fattah and Hanns–Christian Mahler
8 BIOANALYTICAL METHODS AND IMMUNOGENICITY ASSAYS 207
Bonita Rup, Corinna Krinos–Fiorotti, Boris Gorovits, and Hendrik Neubert
9 STRUCTURES AND DYNAMICS OF PROTEINS PROBED BY UV RESONANCE RAMAN SPECTROSCOPY 243
Brian S. Leigh, Diana E. Schlamadinger, and Judy E. Kim
10 FREEZING– AND DRYING–INDUCED MICRO– AND NANO–HETEROGENEITY IN BIOLOGICAL SOLUTIONS 269
Alptekin Aksan, Vishard Ragoonanan, and Carol Hirschmugl
SECTION 3 PHASE III AND COMMERCIAL DEVELOPMENT
11 LATE–STAGE PRODUCT CHARACTERIZATION: APPLICATIONS IN FORMULATION, PROCESS, AND MANUFACTURING DEVELOPMENT 287
Christine P. Chan and Li Shi
12 BIOPHYSICAL ANALYSES SUITABLE FOR CHEMISTRY, MANUFACTURING, AND CONTROL SECTIONS OF THE BIOLOGIC LICENSE APPLICATION (BLA) 317
Zahra Shahrokh, Nazila Salamat–Miller, and John J. Thomas
INDEX 355
